AIDS is an extremely serious and worrying public health problem for many countries throughout the world. In the USA, for example, the official number of AIDS cases is greater than 100,000 and the number of people infected has been estimated at more than 1 million. The propagation of the disease is accentuated by the number of chronic bearers of the virus responsible for AIDS who remain asymptomatic for many years, or even their entire life, and are therefore unidentified sources of infection. This disease, which can be transmitted by sexual contact and via the blood, affects the immune system of the host, thus causing the appearance of opportunistic infections or of pathologies against which the host would have been protected by a healthy immune system. Once AIDS has been recognized, death usually occurs two to three years after diagnosis following a breakdown of the patient's immune defences and multiple opportunistic infections. It is very difficult to classify the AIDS viruses given the extreme genetic and antigenic variability they exhibit; conventionally, it is acknowledged that there are two types of virus responsible for human AIDS: HIV-1 and HIV-2 (human immunodeficiency virus). For a number of reasons, the HIV replication mechanism poses many problems in terms of obtaining effective treatment. This is because proviral DNA, on account of its integration in the cell genome, behaves likes a genetic element of the host. Moreover, the HIV virus is disseminated throughout the entire body in the T lymphocytes, the monocytes, the macrophages and in the central nervous system. Finally, the HIV virus has extremely high antigenic variability. The various curative therapies currently used in clinical medicine consist essentially either in blocking the activity of reverse transcriptase or in inhibiting the activity of viral enzymes that are indispensable for infection or replication (proteases, integrases). The effectiveness of these therapies remains limited since the absorption of these antivirals causes side effects. Moreover, given the high rate of mutation of the HIV virus, the latter rapidly becomes resistant to drugs, such as AZT and other nucleotide analogues, during therapy. The emergence of resistant strains makes it necessary to increase the therapeutic doses administered to patients. Failure of current curative therapies therefore means that it is necessary to develop new therapeutic strategies for fighting retroviral infection.
In their research to develop new curative strategies, the inventors have been led to study the HIV-positive populations who are infected with HIV but are non-progressors, that is to say have not developed AIDS. They have thus been able to show for the first time that in these HIV-positive patients who are infected with HIV classified as non-progressors there is a particular variant of IgG3. The inventors have shown that this variant of IgG3 differs by its primary structure of lower molecular weight, its longer half-life and its higher serum concentration than in the case of conventional IgG3s. The immunoglobulin IgG3 demonstrated by the inventors, which has been isolated and purified, appears to be a protective marker for AIDS and an agent which neutralizes the causative agent of this disease.
Human immunoglobulin IgGs can be divided into four subclasses (IgG1, IgG2, IgG3, IgG4) which differ by minor differences in the primary structure of their heavy chain. The main differences concern the hinge region and the number of inter-chain disulphide bridges. Thus, the hinge region of IgG3 is very long, which accounts for its higher molecular weight (170 kDa) and certain biological properties such as its half-life (in days) which is much shorter for immunoglobulin IgG3s (7 days) than for the other IgG subclasses which have a half-life of around 20 days. IgG3s are capable of selectively binding to certain receptors to the Fc fragment of immunoglobulins such as RFcγI, RFcγIIa, RFcγIIIa. Immunoglobulins, the primary function of which is to bind the antigen so as to neutralize it, also have the role of activating secondary effector functions in particular by way of the complement. The complement system, which is a complex group of serum proteins involved in inflammatory reactions, is one of the most important effector mechanisms for human IgG1s, IgG3s and IgGMs. After having bound the antigen, the IgG1s, IgG3s and IgGMs can activate the enzymatic cascade in the conventional manner of the complement known as C1q, IgG2s for their part being relatively ineffective and IgG4s being incapable of doing so. The binding of C1q to the immunoglobulin is the first step in the cascade of the complement which leads to cell lysis. This mechanism is particularly important for fighting infectious and viral diseases such as AIDS, for example, and plays a crucial role in destroying infected cells.